Cholinergic Contributions to Supramodal Attentional Processes in Rats

Cholinergic neurotransmission has been shown to play an important role in modulating attentional processing of visual stimuli. However, it is not yet clear whether the neurochemical acetylcholine (ACh) is necessary exclusively for visual attention, or if it also contributes to attentional functions through some modality-independent (supramodal) mechanism. To answer this question, we examined the effects of reduced cortical cholinergic afferentation on both a traditional visual and a novel olfactory five-choice serial reaction time task (5-CSRTT), the benchmark rodent test of sustained attention in rats. Following the successful acquisition of both modalities of the task, the rats underwent either a cholinergic immunotoxic- or sham-lesion surgery of the nucleus basalis magnocellularis (NBM), the basal forebrain nuclei that provide the majority of neocortical ACh. Reduced cholinergic afferentation to the neocortex was induced by bilaterally infusing the cholinergic immunotoxin 192 IgG-saporin into the NBM. After surgery, ACh-NBM-lesioned rats performed comparably to sham-lesioned rats under the conditions of low attentional demand, but displayed behavioral decrements relative to the sham-lesioned rats when the attentional demands of the task were increased. Moreover, this decrement in attentional functioning correlated significantly with the number of choline acetyltransferase-immunoreactive cells in the NBM. Importantly, the nature of this behavioral decrement was identical in the visual and olfactory 5-CSRTTs. Together, these data suggest the presence of a supramodal attentional modulatory cortical network whose activity is dependent on cholinergic innervation from the NBM.

[1]  P. Holland,et al.  Removal of Cholinergic Input to Rat Posterior Parietal Cortex Disrupts Incremental Processing of Conditioned Stimuli , 1998, The Journal of Neuroscience.

[2]  M. Sarter,et al.  Interactions between aging and cortical cholinergic deafferentation on attention☆ , 2002, Neurobiology of Aging.

[3]  C. Aoki,et al.  Muscarinic acetylcholine receptors in macaque V1 are most frequently expressed by parvalbumin‐immunoreactive neurons , 2008, The Journal of comparative neurology.

[4]  E. De Rosa,et al.  Cholinergic influences on feature binding. , 2007, Behavioral neuroscience.

[5]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[6]  M. Sarter,et al.  Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention , 2002, Neuroscience.

[7]  S. Devore,et al.  Noradrenergic and cholinergic modulation of olfactory bulb sensory processing , 2012, Frontiers in Behavioral Neuroscience.

[8]  M. Shoaib,et al.  Nicotine improves performance in an attentional set shifting task in rats , 2013, Neuropharmacology.

[9]  R. Marrocco,et al.  Cholinergic modulation of covert attention in the rat , 2001, Psychopharmacology.

[10]  T. Robbins,et al.  Distinct Changes in Cortical Acetylcholine and Noradrenaline Efflux during Contingent and Noncontingent Performance of a Visual Attentional Task , 2001, The Journal of Neuroscience.

[11]  G. Higgins,et al.  A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG‐saporin lesions of the nucleus basalis and/or the septal region , 2003, The European journal of neuroscience.

[12]  R. Galani,et al.  Attention and memory in aged rats: Impact of lifelong environmental enrichment , 2011, Neurobiology of Aging.

[13]  C. Linster,et al.  Characterization of the synaptic properties of olfactory bulb projections. , 2004, Chemical senses.

[14]  Jean-Christophe Cassel,et al.  Hebb-Williams performance and scopolamine challenge in rats with partial immunotoxic hippocampal cholinergic deafferentation , 2005, Brain Research Bulletin.

[15]  J. Muir,et al.  Reversal of visual attentional dysfunction following lesions of the cholinergic basal forebrain by physostigmine and nicotine but not by the 5-HT3 receptor antagonist, ondansetron , 1995, Psychopharmacology.

[16]  William E. Semple,et al.  Metabolic brain pattern of sustained auditory discrimination , 2004, Experimental Brain Research.

[17]  M. Sarter,et al.  The effects of manipulations of attentional demand on cortical acetylcholine release. , 2001, Brain research. Cognitive brain research.

[18]  E. Coulson,et al.  The p75 neurotrophin receptor. , 2008, The international journal of biochemistry & cell biology.

[19]  E. Johnson,et al.  Characterization of the binding properties and retrograde axonal transport of a monoclonal antibody directed against the rat nerve growth factor receptor , 1985, The Journal of cell biology.

[20]  M. Hasselmo,et al.  Contribution of the cholinergic basal forebrain to proactive interference from stored odor memories during associative learning in rats. , 2001, Behavioral neuroscience.

[21]  L. Záborszky The modular organization of brain systems. Basal forebrain: the last frontier. , 2002, Progress in brain research.

[22]  H. Fibiger,et al.  The nucleus basalis magnocellularis: The origin of a cholinergic projection to the neocortex of the rat , 1980, Neuroscience.

[23]  B. Everitt,et al.  AMPA-induced excitotoxic lesions of the basal forebrain: a significant role for the cortical cholinergic system in attentional function , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  Louise S. Delicato,et al.  Acetylcholine contributes through muscarinic receptors to attentional modulation in V1 , 2008, Nature.

[25]  M. Posner,et al.  The attention system of the human brain. , 1990, Annual review of neuroscience.

[26]  Matthew W. Lowder,et al.  Attentional demands for demonstrating deficits following intrabasalis infusions of 192 IgG-saporin , 2008, Behavioural Brain Research.

[27]  Pietro Pietrini,et al.  Selective Effects of Cholinergic Modulation on Task Performance during Selective Attention , 2008, Neuropsychopharmacology.

[28]  E. Grove Efferent connections of the substantia innominata in the rat , 1988, The Journal of comparative neurology.

[29]  Robert H. Perry,et al.  Neurotransmitter enzyme abnormalities in senile dementia Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue , 1977, Journal of the Neurological Sciences.

[30]  V. Brown,et al.  Lesions of the basal forebrain impair reversal learning but not shifting of attentional set in rats , 2008, Behavioural Brain Research.

[31]  M. Sarter,et al.  Article Prefrontal Acetylcholine Release Controls Cue Detection on Multiple Timescales , 2022 .

[32]  Larry L. Butcher,et al.  Cholinergic projections from the basal forebrain to frontal, parietal, temporal, occipital, and cingulate cortices: A combined fluorescent tracer and acetylcholinesterase analysis , 1982, Brain Research Bulletin.

[33]  J. McGaughy,et al.  Cholinergic Deafferentation of Prefrontal Cortex Increases Sensitivity to Cross-Modal Distractors during a Sustained Attention Task , 2008, The Journal of Neuroscience.

[34]  T. Robbins,et al.  Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task , 2000, The European journal of neuroscience.

[35]  T. Robbins,et al.  The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry , 2002, Psychopharmacology.

[36]  M. Hasselmo,et al.  High acetylcholine levels set circuit dynamics for attention and encoding and low acetylcholine levels set dynamics for consolidation. , 2004, Progress in brain research.

[37]  M. Sarter,et al.  Increases in cortical acetylcholine release during sustained attention performance in rats. , 2000, Brain research. Cognitive brain research.

[38]  ML Voytko,et al.  Basal forebrain lesions in monkeys disrupt attention but not learning and memory [published erratum appears in J Neurosci 1995 Mar;15(3): following table of contents] , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[39]  Patrik Vuilleumier,et al.  Cholinergic enhancement modulates neural correlates of selective attention and emotional processing , 2003, NeuroImage.

[40]  M. Esiri,et al.  Alzheimer's disease Correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities , 1982, Journal of the Neurological Sciences.

[41]  P J Bushnell,et al.  Selective removal of cholinergic neurons in the basal forebrain alters cued target detection. , 1999, Neuroreport.

[42]  E. De Rosa,et al.  Impaired visual search in rats reveals cholinergic contributions to feature binding in visuospatial attention. , 2012, Cerebral cortex.

[43]  T. Robbins,et al.  Selective Behavioral and Neurochemical Effects of Cholinergic Lesions Produced by Intrabasalis Infusions of 192 IgG-Saporin on Attentional Performance in a Five-Choice Serial Reaction Time Task , 2002, The Journal of Neuroscience.

[44]  M. Raichle,et al.  Localization of a human system for sustained attention by positron emission tomography , 1991, Nature.

[45]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[46]  Trevor W Robbins,et al.  Cortical cholinergic function and deficits in visual attentional performance in rats following 192 IgG-saporin-induced lesions of the medial prefrontal cortex. , 2004, Cerebral cortex.

[47]  Barry J. Everitt,et al.  Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms , 1997, Psychopharmacology.

[48]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[49]  M. Sarter,et al.  The cognitive neuroscience of sustained attention: where top-down meets bottom-up , 2001, Brain Research Reviews.

[50]  C D Frith,et al.  Neural mechanisms involved in the processing of global and local aspects of hierarchically organized visual stimuli. , 1997, Brain : a journal of neurology.

[51]  M. Sarter,et al.  Sustained Visual Attention Performance-Associated Prefrontal Neuronal Activity: Evidence for Cholinergic Modulation , 2000, The Journal of Neuroscience.

[52]  P. Fletcher,et al.  The 5-HT2A receptor antagonist M100,907 attenuates motor and 'impulsive-type' behaviours produced by NMDA receptor antagonism , 2003, Psychopharmacology.

[53]  F. Gage,et al.  Nerve growth factor receptor and choline acetyltransferase colocalization in neurons within the rat forebrain: Response to fimbria‐fornix transection , 1989, The Journal of comparative neurology.

[54]  S. Mulaik,et al.  Single-sample tests for many correlations. , 1977 .

[55]  B. Bontempi,et al.  Selective immunolesioning of the basal forebrain cholinergic neurons in rats: effect on attention using the 5-choice serial reaction time task , 2002, Psychopharmacology.

[56]  U. Greferath,et al.  The p75 neurotrophin receptor has nonapoptotic antineurotrophic actions in the basal forebrain , 2012, Journal of neuroscience research.

[57]  E. De Rosa,et al.  Cholinergic Deafferentation of the Neocortex Using 192 IgG-Saporin Impairs Feature Binding In Rats , 2009, The Journal of Neuroscience.

[58]  J. Cassel,et al.  Selective cholinergic lesions in the rat nucleus basalis magnocellularis with limited damage in the medial septum specifically alter attention performance in the five-choice serial reaction time task , 2008, Neuroscience.

[59]  E. De Rosa,et al.  A Cross-Species Investigation of Acetylcholine, Attention, and Feature Binding , 2008, Psychological science.

[60]  Trevor W Robbins,et al.  The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats , 2008, Nature Protocols.

[61]  D. Stuss,et al.  Cognitive neuroscience. , 1993, Current opinion in neurobiology.

[62]  J. E CENTRAL CHOLINERGIC PATHWAYS IN THE RAT : AN OVERVIEW BASED ON AN ALTERNATIVE NOMENCLATURE ( Chl-Ch 6 ) , 2002 .